Mindfulness-based Relapse Prevention for Substance Use Disorders: A Systematic Review and Meta-analysis.
Substance use disorder (SUD) is a prevalent health issue with serious personal and societal consequences. This review aims to estimate the effects and safety of Mindfulness-based Relapse Prevention (MBRP) for SUDs. We searched electronic databases for randomized controlled trials evaluating MBRP for adult patients diagnosed with SUDs. Two reviewers independently assessed citations, extracted trial data, and assessed risks of bias. We conducted random-effects meta-analyses and assessed quality of the body of evidence (QoE) using the Grading of Recommendations Assessment, Development, and Evaluation approach. We identified 9 randomized controlled trials comprising 901 participants. We did not detect statistically significant differences between MBRP and comparators on relapse (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.46-1.13, low QoE), frequency of use (standardized mean difference [SMD] 0.02, 95% CI -0.40 to 0.44, low QoE), treatment dropout (OR 0.81, 95% CI 0.40 to 1.62, very low QoE), depressive symptoms (SMD -0.09, 95% CI -0.39 to 0.21, low QoE), anxiety symptoms (SMD -0.32, 95% CI -1.16 to 0.52, very low QoE), and mindfulness (SMD -0.28, 95% CI -0.72 to 0.16, very low QoE). We identified significant differences in favor of MBRP on withdrawal/craving symptoms (SMD -0.13, 95% CI -0.19 to -0.08, I = 0%, low QoE) and negative consequences of substance use (SMD -0.23, 95% CI -0.39 to -0.07, I = 0%, low QoE). We found negligible evidence of adverse events. We have limited confidence in estimates suggesting MBRP yields small effects on withdrawal/craving and negative consequences versus comparator interventions. We did not detect differences for any other outcome. Future trials should aim to minimize participant attrition to improve confidence in effect estimates.


[Postsynaptic metabolic monoamine modulation of effects mediated by NMDA glutamate receptors in spinal motoneurons of the frog].
Monoamines, their agonists and antagonists have been investigated for their influence on responses of spinal motoneurons in frog mediated by NMDA-glutamate receptors (late components of dorsal root polysynaptic EPSP's and depolarizing responses evoked by L-aspartate). Monoamine responses which promoted an increase of intracellular concentration of cAMP and Ca2+ in the motoneurons (activation of alpha- and beta-adrenoreceptors, D1-dopamine and 5-hydroxytryptamine-receptors) reinforced the studied spinal motoneuron responses of frog. These responses were weakened by the monoamine action which led to a decrease of the intracellular concentration of cAMP and Ca2+ (activation of D2-dopamine and 5-hydroxytryptamine1A-receptors). The monoamine effects were inhibited by specific monoamine antagonists, tolbutamide and trifluoperazine. It is supposed that NMDA receptor-channel complex is exposed by cAMP- and Ca(2+)-calmodulin-dependent phosphorylation induced by activation of membrane monoamine receptors.


TQ inhibits hepatocellular carcinoma growth in vitro and in vivo via repression of Notch signaling.
Thymoquinone (TQ) has been reported to possess anti-tumor activity in various types of cancer. However, its effects and molecular mechanism of action in hepatocellular carcinoma (HCC) are still not completely understood. We observed that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2 expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive impact on the Notch pathway, where overexpression of NICD1 reversed the inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2 levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell growth by inducing cell cycle arrest and apoptosis, achieving these effects by repression of the Notch signaling pathway, suggesting that TQ represents a potential preventive or therapeutic agent in HCC patients.


A Fatal Case of Chronic Granulomatous Disease in a Young Man.
Chronic granulomatous disease (CGD) is a rare X-linked or autosomal recessive disorder of early childhood due to defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme in leukocytes. It increases susceptibility to infections by catalase-positive bacteria and fungi. We report a case of an 18-year-old man with CGD who presented to the hospital with septic shock due to bacteremia, pneumonia, and osteomyelitis due to multiple rare microorganisms. Despite aggressive management, he did not survive. Increasing awareness about the common infections in this rare disease, their prevention, and lifelong treatment is warranted.


Total hip/knee arthroplasty in the treatment of tumor-induced osteomalacia patients: More than 1 year follow-up.
Tumor-induced osteomalacia (TIO) may result in a better prognosis after complete resection of the causative neoplasm. However, tumors located proximal to the articular surface of the metaphysis remain largely uninvestigated. A retrospective study of sixteen patients was undertaken to evaluate treatment of tumors with joint arthroplasty and tumor resection. The bone metabolism index, hip/knee joint function, arthroplasty complications and symptoms were followed up for at least 12 months in each patient. All patients presented with neoplasms situated in the articular surface of the metaphysis, with 13 cases undergoing hip arthroplasty and 3 undergoing knee arthroplasty. Treatment of the tumors with joint arthroplasty and tumor resection significantly and rapidly ameliorate bone metabolism indexes in patients with TIO (p<0.01), with no identified tumor recurrence. The joint function evaluation score was improved in 15 patients (93.75%). Complications in these patients included post-operative pain, joint squeaking and secondary hyperparathyroidism. Joint arthroplasty that includes tumor-expanding resection appears to be a safe and appropriate method for the treatment of TIO patients with a neoplasm located in the metaphysis proximal to the articular surface. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Listening to our clients: a dangerous proposal.
Although therapeutic thinking and practice have entered their second century, most practitioners remain largely uncertain as to what data to trust, including "what works" and, "why it works." If anything, practitioners' reliance on ever-increasing numbers of theoretical models and either vague or contradictory research findings as primary guidelines to their practice has added to the confusion. What can the practitioner trust? This paper puts forward the "dangerous proposal" that it is of primary value for clinical professionals to place their trust on an often overlooked variable: the clients' statements about their therapy and their relationship to and with their therapist. It is argued that through the clarification of this variable will emerge a better understanding of the nonspecific variables of the therapeutic relationship itself and, as significantly, of the encompassing interrelational realms of discourse evident in all therapeutic models.


Postpartum blood flow velocity waveforms of the uterine arteries.
Uterine arterial velocity waveforms, recorded by pulsed Doppler technology, demonstrated a significant increase in vascular resistance after the first postpartum day until the fourth to sixth postpartum week. In patients with an isthmic postcesarean hemorrhage, partial placental retention and puerperal endometritis, the corresponding waveforms presented higher diastolic velocity components than was the case for normal puerperal courses, indicating that lower uterine vascular resistance might be associated with these complications.


The Dkk3 gene encodes a vital intracellular regulator of cell proliferation.
Members of the Dickkopf (Dkk) family of Wnt antagonists interrupt Wnt-induced receptor assembly and participate in axial patterning and cell fate determination. One family member, DKK3, does not block Wnt receptor activation. Loss of Dkk3 expression in cancer is associated with hyperproliferation and dysregulated ß-catenin signaling, and ectopic expression of Dkk3 halts cancer growth. The molecular events mediating the DKK3-dependent arrest of ß-catenin-driven cell proliferation in cancer cells are unknown. Here we report the identification of a new intracellular gene product originating from the Dkk3 locus. This Dkk3b transcript originates from a second transcriptional start site located in intron 2 of the Dkk3 gene. It is essential for early mouse development and is a newly recognized regulator of ß-catenin signaling and cell proliferation. Dkk3b interrupts nuclear translocation ß-catenin by capturing cytoplasmic, unphosphorylated ß-catenin in an extra-nuclear complex with ß-TrCP. These data reveal a new regulator of one of the most studied signal transduction pathways in metazoans and provides a novel, completely untapped therapeutic target for silencing the aberrant ß-catenin signaling that drives hyperproliferation in many cancers.


Atopic Eczema: Genetic Associations and Potential Links to Developmental Exposures.
Atopic eczema (AE), or atopic dermatitis (AD), is a common inflammatory skin disease with a disrupted epidermal barrier and an allergic immune response. AD/AE is prominently characterized by a symptomatic itch and transient skin lesions. Infants compose a significant percentage affected. Two models have been proposed to explain AD/AE skin pathology: the gut microbiome-focused inside-outside model and the outside-inside model concentrating on the disrupted skin barrier/skin microbiome. Gene disruptions contributing to epidermal structure, as well as those in immune system genes, are implicated. Over 30 genes have been linked to AD/AE with Flg and Tmem79/Matt alterations being common. Other linked disruptions are in the interleukin-1 family of cytokines/receptors and the TH2 gene family of cytokines. Inheritable epigenetic modifications of the genes or associated proteins may also be involved. Skin barrier disruption and the allergic immune response have been the main foci in mechanistic studies of AD/AE, but the role of the environment is becoming more apparent. Thus, an examination of in utero exposures could be very helpful in understanding the heterogeneity of AD/AE. Although research is limited, there is evidence that developmental exposure to environmental tobacco smoke or phthalates may impact disease. Management for AD/AE includes topical corticosteroids and calcineurin inhibitors, which safely facilitate improvements in select individuals. Disease heterogeneity warrants continued research not only into elucidating disease mechanism(s), via identification of contributing genetic alterations, but also research to understand how/when these genetic alterations occur. This may lead to the cure that those affected by AD/AE eagerly await.


Carbon isotopic record of terrestrial ecosystems spanning the Late Miocene extinction of Oreopithecus bambolii, Baccinello Basin (Tuscany, Italy).
Oreopithecus bambolii is a Late Miocene hominoid with an extensive fossil record in the Baccinello Basin (Tuscany, Italy), and was the only western European hominoid to survive a major extinction event ca. 9.6 Ma (millions of years ago). Oreopithecus lived in the insular Tusco-Sardinian paleobioprovince, where it evolved many unique anatomical specializations that make it important for understanding the mechanisms and history of Late Miocene hominoid evolution. The eventual extinction of Oreopithecus and its associated fauna ca. 6.5 Ma has generally been attributed to interaction with species that arrived from continental Europe following tectonic collision of the Tusco-Sardinian province with mainland Italy, but palynological, paleontological, and sedimentological records indicate an environmental shift toward more variable climate across the extinction event. To explore the possibility of environmental change as a contributing factor in the extinction of Oreopithecus, we developed a stable carbon and oxygen isotope record from organic matter in paleosols from the Baccinello Basin. These data show very low temporal and spatial variability (indicating plant ecosystem stability through time and space) and provide no evidence for ecologically significant changes in floral composition spanning the extinction event, suggesting that environmental change was not an underlying cause for the extinction of Oreopithecus and its associated fauna. The carbon isotope values fall entirely within the range of isotopic variability for modern plants following the C(3) photosynthetic pathway (trees, shrubs, cool-season grasses), indicating that C(4) vegetation (warm-season grasses) was not an important component of biomass. When corrected for temporal variation in the carbon isotopic composition of atmospheric carbon dioxide, the paleosol carbon isotope values are consistent with predicted values based on modern plants and the Baccinello palynoflora, supporting the reliability of paleosol isotopic records as paleoecological proxies.


TNF-alpha inhibits adult fast myosin accumulation in myotubes.
Increased muscle catabolism is frequently observed in association with inflammatory disease. TNF-alpha has been implicated as an important messenger for muscle catabolism. Experiments with cultured muscle cells exposed to TNF-alpha have produced conflicting results. In a mouse cell line (C2C12), effects ranged from catabolic to anabolic. The results reported here offer an explanation for the observed discrepancies. It was found that TNF-alpha induced proliferation of myoblasts in fully differentiated cultures in low serum media and inhibited adult fast myosin accumulation under all conditions that were tested. Furthermore, TNF-alpha caused a proliferation dependent increase in total cell protein. Addition of insulin masked the effect of TNF-alpha on total protein, but not that on adult fast myosin accumulation. Discrepancies between studies can be explained by differences in proliferation rate, the dynamic nature of C2C12 myotube cultures and accumulation of adult fast myosin. The results are consistent with a dual role of TNF-alpha: stimulation of regeneration by short-term exposure and induction of muscle wasting by prolonged exposure.


[Cytoprotection in Cardiology: Achievements and Prospects].
Currently, pharmacotherapy of coronary heart disease, based on antianginal drugs directly improve coronary blood flow, antiplatelet, and lipid-lowering drugs, includes a new class of drugs - cardiocytoprotectors. Recent ischemic cardiomyocytes improve security in the ATP, by optimizing the energy metabolism by reducing the need for oxygen cardiomyocytes and has an antioxidant effect, protecting cellular structures and enzymes from oxidative stress accompanying hypoxia.


[Direct current therapy for local control of malignant tumors].
Sixteen malignant tumors of soft tissue (15 cases) were treated with low voltage direct current (DC therapy) with or without systemic chemotherapy. Two platinum or stainless steel electrodes were placed in the tumor and around 10 volts of direct current was passed for 1 hour. In cases in which chemotherapy was performed, single or combined anticancer agents consisted of ADM and BLM were administered simultaneously with DC therapy by systemic route. Ten cases (11 tumors) out of 15 cases received no other local treatment. Histological examination was performed in 6 of 11 lesions, and in all lesions pathological therapeutic effects were recognized. Decrease in tumor size was observed in 9 lesions. In 2 cases the tumors disappeared completely after DC therapy only. In one case receiving DC therapy with chemotherapy, the tumor decreased dramatically and became resectable. Main complications were slight pain during treatment and slight fever after treatment, but special treatment for these complications was not necessary. Our results suggested that DC therapy with or without systemic chemotherapy was useful for local control of malignant tumors. And also if DC therapy had been performed simultaneously with chemotherapy the therapeutic effects seemed to be more emphasized than single use of these therapies.


Temperature and composition dependence of the Soret coefficient in Lennard-Jones mixtures presenting consolute critical phenomena.
Nonequilibrium molecular dynamics calculations have been carried out o Lennard-Jones binary mixtures with the aim to investigate the dependence of the Soret coefficient on the temperature and on the composition for systems presenting phase transitions. By an appropriate choice of the cross interaction parameter, epsilon(12) (0 < epsilon(12) < min{epsilon(11),epsilon(22)}), these systems show a mixing/demixing (consolute) phase transition. The other parameters are those of a binary mixture of Argon and Krypton. This system has been considered over a wide range of temperatures (up to approximately or equal to 1000 K), of compositions (0.1 < or = x(1) < or = 0.9), and of cross interaction parameter (0 < epsilon(12) < min{epsilon(11),epsilon(22)}). The study allows the formulation of a very simple expression for the Soret coefficient, S(T), as a function of temperature and composition. Indeed the computed values of S(T) in the one phase region outside the critical region are closely fitted by the function [T-T(c)(x(1))](-1) where T(c)(x(1)) is the demixing temperature of the mixture under study. This result indicates for this type of systems a dependence of S(T), as a function of the temperature, on a unique characteristic property of the fluid mixture, the demixing temperature T(c), which, in turn, is a function of the binary mixture composition x(1).


Regulation of nitric oxide consumption by hypoxic red blood cells.
The homeostasis of nitric oxide (NO) is attained through a balance between its production and consumption. Shifts in NO bioavailability have been linked to a variety of diseases. Although the regulation of NO production has been well documented, its consumption is largely thought to be unregulated. Here, we have demonstrated that under hypoxic conditions, NO accelerates its own consumption by increasing its entry into RBCs. When RBCs were exposed to NO (1:400 NO/heme ratio) under hypoxic conditions to form HbFe(II)NO, the consumption rate of NO increased significantly. This increase in NO consumption converted the bioactivity of serotonin from a vasodilator to a vasoconstrictor in isolated coronary arterioles. We identified HbFe(II)NO as a potential mediator of accelerated NO consumption. Accelerated NO consumption by HbFe(II)NO-bearing RBCs may contribute to hypoxic pulmonary vasoconstriction and the rebound effect seen on termination of NO inhalation therapy. Furthermore, accelerated NO consumption may exacerbate ischemia-mediated vasospasm and nitrate tolerance. Finally, this phenomenon may be an evolved mechanism to stabilize the vasculature in sepsis.


Hunting increases adaptive auditory map plasticity in adult barn owls.
The optic tectum (OT) of barn owls contains topographic maps of auditory and visual space. Barn owls reared with horizontally displacing prismatic spectacles (prisms) acquire a novel auditory space map in the OT that restores alignment with the prismatically displaced visual map. Although juvenile owls readily acquire alternative maps of auditory space as a result of experience, this plasticity is reduced greatly in adults. We tested whether hunting live prey, a natural and critically important behavior for barn owls, increases auditory map plasticity in adult owls. Two groups of naive adult owls were fit with prisms. The first group was fed dead mice during 10 weeks of prism experience, while the second group was required to hunt live prey for an identical period of time. When the owls hunted live prey, auditory maps shifted substantially farther (five times farther, on average) and the consistency of tuning curve shifts within each map increased. Only a short period of time in each day, during which the two groups experienced different conditions, accounts for this effect. In addition, increased map plasticity correlated with behavioral improvements in the owls' ability to strike and capture prey. These results indicate that the experience of hunting dramatically increases adult adaptive plasticity in this pathway.


Posterior and Anterior Fusion for Severe Cervical Kyphosis in a Patient with Chondrodysplasia Punctata: A Case Report.
A 4-year-old girl with spastic gait and hand clumsiness who was diagnosed with cervical myelopathy caused by atlantoaxial dislocation and midcervical severe kyphosis associated with chondrodysplasia punctata (CDP). The patient underwent posterior instrumentation and anterior spinal fusion and successful correction with osseous fusion was obtained 8 months after surgery. In addition, the preoperative neurological symptoms were completely recovered. Owing to the characteristics of CDP, the treatment for the cervical lesion is extremely complicated. Successful stabilization and improvement of the neurological symptom were achieved by combining posterior and anterior fusion with instrumentation in this case.


Role of the alpha subunit cytoplasmic domain in regulation of adhesive activity mediated by the integrin VLA-2.
To investigate the role of the alpha subunit cytoplasmic domain in the regulation of VLA-2 functional activity, we expressed several chimeric and deleted forms of the alpha 2 subunit in two different human cell lines, K562 and RD. Each mutant construct formed surface VLA-2 heterodimers as efficiently as wild type alpha 2 subunit, except for a construct (X2CO1127) truncated just before the consensus GFFKR cytoplasmic domain motif, that was not expressed at the cell surface. Truncation of the alpha 2 cytoplasmic domain just after the GFFKR motif resulted in a complete loss of constitutive activity of VLA-2 in RD cells. If the integrin was already constitutively inactive, as in K562 cells, the cytoplasmic domain deletion had no effect. In both K562 and RD cells, cytoplasmic tail deletion eliminated up-regulation of adhesion in response to the phorbol ester, phorbol 12-myristate 13-acetate (PMA). In comparison, exchange of the alpha 2 cytoplasmic domain with the alpha 4 or alpha 5 cytoplasmic domains had no effect on constitutive activity (in RD cells), or on constitutive inactivity (in K562 cells) and did not eliminate PMA-stimulated activity (in K562 or RD cells). These results clearly demonstrate that the cytoplasmic domain of an alpha chain (not necessarily from alpha 2 itself) is required to maintain VLA-2 constitutive activity and to allow a responsiveness to PMA stimulation. In cases where VLA-2 was either constitutively inactive (as in K562 cells) or inactive due to cytoplasmic domain deletion (e.g. in RD cells), agents such as Mn2+ or the anti-beta 1 monoclonal antibody TS2/16 caused a marked increase in adhesive function, thus proving that the integrins were not irreversibly inactive, and that cellular regulatory constraints could be bypassed by extracellular stimuli.


Antitumor activity of the third generation EphA2 CAR-T cells against glioblastoma is associated with interferon gamma induced PD-L1.
Glioblastoma (GBM) is the most common and aggressive brain malignancy in adults and is currently incurable with conventional therapies. The use of chimeric antigen receptor (CAR) modified T cells has been successful in clinical treatment of blood cancers, except solid tumors such as GBM. This study generated two third-generation CARs targeting different epitopes of ephrin type-A receptor 2 (EphA2) and examined their anti-GBM efficacy in vitro and in tumor-bearing mice. We observed that these two types of T cells expressing CAR (CAR-T) targeting EphA2 could be activated and expanded by EphA2 positive tumor cells in vitro. The survival of tumor-bearing mice after EphA2 CAR-T cell treatment was significantly improved. T cells transduced with one of the two EphA2 CARs exhibited better anti-tumor activity, which is related to the upregulation of CXCR-1/2 and appropriate interferon-γ (IFN-γ) production. CAR-T cells expressed excessively high level of IFN-γ exhibited poor anti-tumor activity resulting from inducing the upregulation of PD-L1 in GBM cells. The combination of CAR-T cells with poor anti-tumor activity and PD1 blockade improved the efficacy in tumor-bearing mice. In conclusion, both types of EphA2 CAR-T cells eliminated 20%-50% of GBM in xenograft mouse models. The appropriate combination of IFN-γ and CXCR-1/2 levels is a key factor for evaluating the antitumor efficiency of CAR-T cells.


Fecal intestinal alkaline phosphatase: a parameter for toxic damage of the small intestinal mucosa.
An immunoprecipitation procedure is presented for the measurement of rat intestinal alkaline phosphatase (I-AP) in feces. Controls exhibit a logarithmic normal distribution of fecal I-AP. Single administration of an agent toxic for small intestinal mucosa like bleomycin or triparanol induces an increase of fecal I-AP on the 1st day and a marked reduction of I-AP activity on the following 3 days. After the 5th day, abnormal high fecal I-AP activities were observed during regeneration. In parallel, morphometry and measurements of I-AP activity in the homogenate of small intestinal mucosa were performed. Rat fecal I-AP excretion proved to be a simple, non-invasive, sensitive marker for toxic damage of the small intestinal mucosa.


Radio frequency identification technology reduce intravenous thrombolysis time in acute ischemic stroke.
To inspect whether time management with radio frequency identification technology (RFID) reduces symptom onset-to-intravenous thrombolysis time (OTT) in acute ischemic stroke (AIS). In the retrospective study, patients with AIS, transferred by Emergency Medical Services (EMS) to Hunan Provincial People's Hospital between September 2019 to June 2022, divided into three groups, as traditional group, in-hospital RFID group and whole process RFID group. Baseline characteristics and time metrics were compared. After the whole emergency process applied with RFID time management, Door to intravenous thrombolysis time (DNT) was reduced from 125.00±43.16 min to 32.59±25.45 min (F = 121.857, p<0.001), and OTT was reduced from 235.53±57.27 min to 144.31±47.96 min (F = 10.377, p<0.001). Time management with RFID is effective in reducing OTT in AIS patients with thrombolysis treatment.


A United States perspective on long-term management of areas contaminated with radioactive materials.
The US has far-reaching and extensive experience in the long-term management of areas contaminated with radioactive materials. This experience base includes the Department of Energy's continued follow-up with Hiroshima and Nagasaki from the 1940s at the Radiological Effects Research Foundation in Hiroshima, Japan, the long-term management of the Marshall Islands Programme, the clean-up of the US nuclear weapons complex and the ongoing management of accident sites such as in Palomares, Spain. This paper discusses the lessons learnt and best practices gained from this far-reaching and extensive experience in the long-term management of areas contaminated with radioactive materials.


How Healthy Aging and Contact With Children Are Associated With Satisfaction in Middle-Aged and Older Parents in China: A Mediation Analysis.
This study aims to examine the mediation role of satisfaction with children on the association between contact with children (CCT) and healthy aging among middle-aged and older parents in China. Data from 9,575 parents over 45 years old were obtained from the 2018 China Health and Retirement Longitudinal Survey. A multinomial logistic regression model was applied to measure the association between contact, satisfaction, and healthy aging with potential confounders controlled. We used the Sobel-Goodman Mediation test to analyze the mediation role of satisfaction on the association between types of CCT and healthy aging. Parents with contact with adult children had higher satisfaction with children [for contact weekly (satisfied/unsatisfied): relative risk ratio (RRR) = 2.44, CI = 1.92-3.10] and higher healthy aging [for contact weekly (Q5/Q1): RRR = 1.41, CI = 1.13-1.77]. Satisfaction was strongly related to healthy aging [for satisfied (Q5/Q1): RRR = 3.44, CI = 2.14-5.51], and mediated 19.05% of healthy aging for weekly contact (Sobel test z = 4.338; indirect role = 0.014, CI = 0.011-0.018; direct role = 0.061, CI = 0.029-0.094). Subgroup analysis further revealed that satisfaction with contact played a partial mediating role between monthly contact and healthy aging in female and rural groups. Monthly CCT is more appropriate for older parents. Satisfaction with children in older parents seems to act as a significant and partial mediator of the relationship between contact and healthy aging. The contribution of satisfaction to healthy aging could be important to be considered and promoted in women and rural older parents, independent of CCT.


Application of enhanced recovery after surgery in perioperative patients undergoing laparoscopic surgery for gastric cancer: A meta-analysis.
To analyze the effect of enhanced recovery after surgery (ERAS) in perioperative patients undergoing laparoscopic surgery for gastric cancer (GC). We searched the literature databases of PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Web of Science (https://www.webofscience.com/) for studies related to ERAS and laparoscopic surgery for GC from their inception till October 2022, and the retrieved articles were further screened for analysis. The literature quality was evaluated based on the Cochrane risk of bias tool. The endpoints included the first postoperative exhaust time, first postoperative bowel movement, length of stay, complications and hospitalization expenses. The meta-analysis was performed using RevMan 5.4 software. 11 studies were included, involving 2039 patients. Meta-analysis showed that the first postoperative exhaust and bowel movement were earlier and the length of stay was shorter in the experimental group (e.g.,) than in the control group (CG) (P < .05). Moreover, a lower incidence of complications and markedly reduced hospitalization expenses were determined in for example (P < .05). Due to the heterogeneity in the comparison of indicators such as the first postoperative exhaust and bowel movement across articles, a funnel plot was drawn for observations. The plot was found to be basically symmetrical, indicating small results bias and reliable reference significance of our findings. ERAS for perioperative patients undergoing laparoscopic surgery for GC can effectively shorten the postoperative rehabilitation cycle of patients, improve surgical safety and reduce treatment costs.


A study on regional differences in decidualization of the mouse uterus.
Although regional differences in mouse decidualization have been recognized for decades, the molecular mechanisms remain understudied. In the present study, by using RNA-seq, we compared transcriptomic differences between the anti-mesometrial (AM) region and the mesometrial (M) region of mouse uterus on day 8 of pregnancy. A total of 1423 differentially expressed genes were identified, of which 811 genes were upregulated and 612 genes were downregulated in the AM region compared to those in the M region. Gene ontology analysis showed that upregulated genes were generally involved in cell metabolism and differentiation, whereas downregulated genes were associated with lymphocyte themes and immune response. Through network analysis, we identified a total of 6 hub genes. These hub genes are likely more important than other genes due to their key positions in the network. We also examined the promoter regions of differentially expressed genes for the enrichment of transcription factor-binding sites. In the end, we demonstrated that a similar regional gene expression pattern can be observed in the artificial decidualization model. Our study contributes to an increase in the knowledge on the molecular mechanisms underlying regional decidualization in mice.


Post-traumatic stress disorder in the military veteran.
1. Military personnel exposed to war-zone trauma are at risk for developing PTSD. Those at greatest risk are those exposed to the highest levels of war-zone stress, those wounded in action, those incarcerated as prisoners of war, and those who manifest acute war-zone reactions, such as CSR. 2. In addition to problems directly attributable to PTSD symptoms per se, individuals with this disorder frequently suffer from other comorbid psychiatric disorders, such as depression, other anxiety disorders, and alcohol or substance abuse/dependence. The resulting constellation of psychiatric symptoms frequently impairs marital, vocational, and social function. 3. The likelihood of developing chronic PTSD depends on premilitary and postmilitary factors in addition to features of the trauma itself. Premilitary factors include negative environmental factors in childhood, economic deprivation, family psychiatric history, age of entry into the military, premilitary educational attainment, and personality characteristics. Postmilitary factors include social support and the veteran's coping skills. 4. Among American military personnel, there are three populations at risk for unique problems that may amplify the psychological impact of war-zone stress. They are women whose war-zone experiences may be complicated by sexual assault and harassment; nonwhite ethnic minority individuals whose premilitary, postmilitary, and military experience is affected by the many manifestations of racism; and those with war-related physical disabilities, whose PTSD and medical problems often exacerbate each other. 5. The longitudinal course of PTSD is quite variable. Some trauma survivors may achieve complete recovery, whereas others may develop a persistent mental disorder in which they are severely and chronically incapacitated. Other patterns include delayed, chronic, and intermittent PTSD. 6. Theoretically primary preventive measures might include prevention of war or screening out vulnerable military recruits. In practice, primary preventive measures have included psychoeducational and inoculation approaches. Secondary prevention has been attempted through critical incident stress debriefing administered according to the principles of proximity, immediacy, expectancy, and simplicity. Tertiary prevention has included psychotherapy, pharmacotherapy, dual diagnosis approaches, peer counseling, and inpatient treatment. Few treatments have been rigorously evaluated. 7. There are both theoretical reasons and empirical findings to suggest that military veterans with PTSD are at greater risk for more physical health problems, poorer health status, and more medical service usage. Much more research is needed on this matter. 8. Despite the potential adverse impact of war-zone exposure on mental and physical health, there is also evidence that trauma can sometimes have salutary effects on personality and overall function.


Dysregulation in T helper 1/T helper 2 cytokine ratios in patients with multiple myeloma.
We have assessed alterations of Th1 and Th2 derived cytokines in the progression of multiple myeloma (MM) by determining their circulatory concentrations in patients with MM and healthy controls and correlated observations with grade and severity of the disease. The study group consisted of 112 subjects: 62 patients with MM and 50 healthy controls. Regarding serum levels of Th1 cytokines, IFN-gamma was significantly lower and IL-2 was non-significantly increased, while regarding levels of Th2 cytokines, IL-4 and IL-10 were significantly elevated. Results of our study indicate that a marked polarization exists toward Th2 cytokines in MM while Th1 cytokines remain suppressed.


Alterations of Vertical Jump Mechanics after a Half-Marathon Mountain Running Race.
The fatiguing effect of long-distance running has been examined in the context of a variety of parameters. However, there is scarcity of data regarding its effect on the vertical jump mechanics. The purpose of this study was to investigate the alterations of countermovement jump (CMJ) mechanics after a half-marathon mountain race. Twenty-seven runners performed CMJs before the race (Pre), immediately after the race (Post 1) and five minutes after Post 1 (Post 2). Instantaneous and ensemble-average analysis focused on jump height and, the maximum peaks and time-to-maximum peaks of: Displacement, vertical force (Fz), anterior-posterior force (Fx), Velocity and Power, in the eccentric (tECC) and concentric (tCON) phase of the jump, respectively. Repeated measures ANOVAs were used for statistical analysis (p ≤ 0.05). The jump height decrease was significant in Post 2 (-7.9%) but not in Post 1 (-4.1%). Fx and Velocity decreased significantly in both Post 1 (only in tECC) and Post 2 (both tECC and tCON). Α timing shift of the Fz peaks (earlier during tECC and later during tCON) and altered relative peak times (only in tECC) were also observed. Ensemble-average analysis revealed several time intervals of significant post-race alterations and a timing shift in the Fz-Velocity loop. An overall trend of lowered post-race jump output and mechanics was characterised by altered jump timing, restricted anterior-posterior movement and altered force-velocity relations. The specificity of mountain running fatigue to eccentric muscle work, appears to be reflected in the different time order of the post-race reductions, with the eccentric phase reductions preceding those of the concentric one. Thus, those who engage in mountain running should particularly consider downhill training to optimise eccentric muscular action. Key pointsThe 4.1% reduction of jump height immediately after the race is not statistically significantThe eccentric phase alterations of jump mechanics precede those of the concentric ones.Force-velocity alterations present a timing shift rather than a change in force or velocity magnitude.


The influence of polytypic structures on the M011-->M101 solid-solid phase transition of n-C36H74: an application of the oblique infrared transmission method.
The molecular displacements on the M011-->M101 phase transition of n-hexatriacontane (n-C36H74) have been investigated with an IR microscope designed for the oblique infrared transmission method. It has been clarified that two polytypic structures of the M011 modification, single-layered structure (Mon) and double-layered one (Orth II), both transform to the M101 modification of single-layered structure with their respective mechanisms. On the M011(Mon)-->M101 transition, the inclination direction of molecular axis is changed by 90 degrees through an intermediate state in which the molecular chain is set perpendicular to the basal plane of the single crystal. On the other hand, a polymorphic-polytypic composite structural change on the M011(Orth II)-->M101 transition is accomplished through two kinds of molecular displacements occurring alternately along the stacking direction of molecular layers.


Approach to Highly Sensitized Kidney Transplant Candidates and a Positive Crossmatch.
Human leukocyte antigen (HLA)-incompatible kidney transplantation offers survival benefit compared with ongoing dialysis. There have been considerable advances in the last decade to allow for increased access to transplant for the HLA-sensitized kidney transplant candidates. These include increased priority in the kidney allocation system, kidney paired donation, and novel desensitization strategies. A better understanding of the role of B cells, plasma cells, and complement and inflammatory cytokines in the pathophysiology of HLA antibody-mediated allograft injury has led to the use of novel therapeutics for desensitization and treatment of antibody-mediated rejection. Here we discuss current approaches to kidney transplantation in HLA-sensitized kidney transplant candidates.


Renal ectopic lipid deposition in rats with early-stage diabetic nephropathy evaluated by the MR mDixon-Quant technique: association with the expression of SREBP-1 and PPARα in renal tissue.
Renal ectopic lipid deposition (ELD) plays a significant role in the development of diabetic nephropathy (DN). This study aimed to use the magnetic resonance (MR) mDixon-Quant technique to evaluate renal ELD and its association with the expression of sterol regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor alpha (PPARα) in renal tissue. Seventy male Sprague-Dawley (SD) rats were randomly divided into experimental (n=50) and control groups (n=20). A high-fat diet combined with low-dose streptozotocin (STZ) was administered to the experimental group to establish a type 2 diabetes mellitus (T2DM) model. The rats received renal mDixon-Quant scans and blood lipid and histopathological examinations in batches after the T2DM model was established. According to the histopathological findings, the included rats were stratified into control and early DN groups. Renal fat fraction (FF), blood lipid level, the ratio of the integrated optical density of intracellular lipid droplets and the total area of all the cells (IOD/TAC), and the expression of SREBP-1 and PPARɑ in renal tissue were analyzed. Compared to the controls, renal FF, IOD/TAC, the expression of SREBP-1 in renal tissue, and serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels were higher in the early DN group, while the expression of PPARɑ in renal tissue and the high-density lipoprotein (HDL) level were lower (all P values <0.001). Renal FF gradually increased with the progression of disease [r=0.810 (95% CI: 0.675-0.928), P<0.001]. Positive correlations between renal FF and each of the following: TC, TG, LDL, IOD/TAC, and the expression of SREBP-1 [r=0.479 (95% CI: 0.353-0.640, P=0.012), 0.576 (95% CI: 0.283-0.842, P=0.002), 0.441 (95% CI: 0.305-0.606, P=0.021), 0.911 (95% CI: 0.809-0.964, P<0.001) and 0.800 (95% CI: 0.640-0.910, P<0.001), respectively] and negative correlations between renal FF and each of the following: HDL and the expression of PPARɑ [r=-0.611 (95% CI: -0.809 to -0.469, P=0.001) and -0.748 (95% CI: -0.886 to -0.585, P<0.001), respectively] were found. Renal lipid deposition evaluated by the MR mDixon-Quant technique is associated with the blood lipid level, histological fat quantification, and the expression of SREBP-1 and PPARɑ in renal tissue. The renal FF value might serve as a biomarker for better understanding of renal lipid metabolism in early-stage DN.


Obesity development in neuron-specific lipoprotein lipase deficient mice is not responsive to increased dietary fat content or change in fat composition.
We have previously reported that mice with neuron-specific LPL deficiency (NEXLPL-/-) become obese by 16weeks of age on chow. Moreover, these mice had reduced uptake of triglyceride (TG)-rich lipoprotein-derived fatty acids and lower levels of n-3 long chain polyunsaturated fatty acids (n-3 PUFAs) in the hypothalamus. Here, we asked whether increased dietary fat content or altered dietary composition could modulate obesity development in NEXLPL-/- mice. Male NEXLPL-/- mice and littermate controls (WT) were randomly assigned one of three synthetic diets; a high carbohydrate diet (HC, 10% fat), a high-fat diet (HF, 45% fat), or a HC diet supplemented with n-3 PUFAs (HCn-3, 10% fat, Lovaza, GSK®). After 42weeks of HC feeding, body weight and fat mass were increased in the NEXLPL-/- mice compared to WT. WT mice fed a HF diet displayed typical diet-induced obesity, but weight gain was only marginal in HF-fed NEXLPL-/- mice, with no significant difference in body composition. Dietary n-3 PUFA supplementation did not prevent obesity in NEXLPL-/- mice, but was associated with differential modifications in hypothalamic gene expression and PUFA concentration compared to WT mice. Our findings suggest that neuronal LPL is involved in the regulation of body weight and composition in response to either the change in quantity (HF feeding) or quality (n-3 PUFA-enriched) of dietary fat. The precise role of LPL in lipid sensing in the brain requires further investigation.


Further purification and characterization of macromomycin.
The antitumor polypeptide, macromomycin (MCR) produced by Streptomyces macromomyceticus, was purified by ammonium sulfate precipitation, ultrafiltration and chromatographic techniques using Amberlite IRA-410, DEAE Sephadex A-25 (CI- and OH-type) and Sephadex G-50. Purified MCR was obtained as a white powder by lyophilization. MCR, thus purified, exhibited a single peak on Sephadex G-50 chromatography with no detectable contaminant by ultracentrifugation and polyacrylamide gel electrophoresis. MCR is an acidic polypeptide having an isoelectric point of pH 5.4. It contains no arginine and methionine. The molecular weight was 11,700, 12,500 and 11,400 by amino acid composition, gel filtration and analytical ultracentrifugation, respectively. MCR is labile as a lyophilized powder but is successfully stabilized by the addition of maltose.


Lymph node tissue kallikrein-related peptidase 6 mRNA: a progression marker for colorectal cancer.
A most important characteristic feature for poor prognosis in colorectal cancer (CRC) is the presence of lymph node metastasis. Determination of carcinoembryonic antigen (CEA) mRNA levels in lymph nodes has proven powerful for quantification of disseminated tumour cells. Here, we investigate the utility of human tissue kallikrein-related peptidase 6 (KLK6) mRNA as a progression biomarker to complement CEA mRNA, for improved selection of patients in need of adjuvant therapy and intensified follow-up after surgery. Lymph nodes of pTNM stage I-IV CRC- (166 patients/503 lymph nodes) and control (23/108) patients were collected at surgery and analysed by quantitative RT-PCR. Lymph node KLK6 positivity was an indicator of poor outcome (hazard ratio 3.7). Risk of recurrence and cancer death increased with KLK6 lymph node levels. Patients with KLK6 lymph node levels above the 90th percentile had a hazard ratio of 6.5 and 76 months shorter average survival time compared to patients with KLK6 negative nodes. The KLK6 positivity in lymph nodes with few tumour cells, that is, low CEA mRNA levels, also indicated poor prognosis (hazard ratio 2.8). In CRC patients, lymph node KLK6 positivity indicated presence of aggressive tumour cells associated with poor prognosis and high risk of tumour recurrence.


Postoperative intra-abdominal adhesions: a personal view.
This paper reviews a near half century of interest and personal involvement in the topic of intra-abdominal adhesions. During this time, much has been learned about the aetiology of this condition, which results from the presence of ischaemic or foreign material in the peritoneal cavity. This knowledge, in turn, has led to modifications in our operative practices. While for many years a rather neglected subject, recent studies have stressed the complications that may result from adhesions, in particular small bowel obstruction, and have documented the clinical burden of adhesions on the health services. For over a century, surgeons have investigated means of preventing or at least modifying the formation of adhesions. At first, these were carried out in a quite arbitrary manner, but in more recent times, there has been a more rational approach, based on our clearer knowledge of their aetiology.


Adaption of Maximal Glycolysis Rate after Resistance Exercise with Different Volume Load.
The aim of this study was to investigate the effect of six-weeks of resistance training with different volume load on the maximum glycolysis rate. 24 male strength-trained volunteers were assigned in a high volume low load (50% of their 1RM with 5 sets and reps up to muscle failure) and a low volume high load (70% of their 1RM with 5 sets of ten reps) resistance exercise group. The resistance training performed 3 days per week over 6 weeks. The maximum glycolysis rate was determined using isokinetic force testing before and after the intervention. There was a significant increase in glycolysis rate over the training period across all subjects (p=0.032). High volume low load exercise increased significantly from 0.271±0.067 mmol·l -1 ·s -1 to 0.298±0.067 mmol·l -1 ·s -1 (p=0.022) and low volume high load exercise showed no significant changes from 0.249±0.122 mmol·l -1 ·s -1 to 0.291±0.089 mmol·l -1 ·s -1 (p=0.233). No significant effect on glycolysis rate was observed between the training groups (p=0.650). Resistance training increases glycolysis rate regardless of volume load.


A rare case of penile metastasis of testicular cancer presented with priapism.
Priapism is thought as a condition of penile erection that persists beyond or is unrelated to sexual stimulation. Commonly two different entities of priapism are known, one is low-flow priapism and the other is high-flow priapism. It is important to distinguish these two conditions for the subsequent different treatments. We report a rare case of an indistinguishable priapism caused by penile metastasis of testicular cancer.


Efficacy and Safety of Crisaborole Ointment, 2%, for the Treatment of Mild-to-Moderate Atopic Dermatitis Across Racial and Ethnic Groups.
Atopic dermatitis is highly prevalent in black/African American, Asian, and Hispanic patients, making assessment of these populations in clinical trials important. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. In two pivotal phase III clinical trials in patients aged ≥ 2 years, crisaborole was superior to vehicle in reducing global disease severity. The most common treatment-related adverse event was application site pain. The objective of this study was to investigate the efficacy and safety of crisaborole according to patient race and ethnicity. A pooled post hoc analysis by race and ethnicity of the two pivotal trials and a safety extension trial was performed. Race included white or nonwhite (encompassing Asian/native Hawaiian/other Pacific Islander, black/African American, and other/American Indian/Alaskan native); ethnicity included Hispanic/Latino or not Hispanic/Latino. In white, nonwhite, Hispanic/Latino, and not Hispanic/Latino groups at day 29, more crisaborole- than vehicle-treated patients achieved improvements in global disease severity [Investigator's Static Global Assessment of clear/almost clear with a ≥ 2-grade improvement (white: 33.5% vs. 22.3%, nominal p < 0.001; nonwhite: 30.0% vs. 21.3%, nominal p < 0.05; Hispanic/Latino: 35.4% vs. 18.2%, nominal p < 0.01; not Hispanic/Latino: 31.3% vs. 22.8%, nominal p < 0.01)]. Crisaborole treatment also improved atopic dermatitis signs/symptoms and quality of life. Frequency of crisaborole-related adverse events was 7.1-8.5% in the pivotal trials. Across races and ethnicities, crisaborole demonstrated efficacy for the treatment of mild-to-moderate atopic dermatitis, with a low frequency of treatment-related adverse events.


Colossal Magnetoresistance in a Mott Insulator via Magnetic Field-Driven Insulator-Metal Transition.
We present a new type of colossal magnetoresistance (CMR) arising from an anomalous collapse of the Mott insulating state via a modest magnetic field in a bilayer ruthenate, Ti-doped Ca_{3}Ru_{2}O_{7}. Such an insulator-metal transition is accompanied by changes in both lattice and magnetic structures. Our findings have important implications because a magnetic field usually stabilizes the insulating ground state in a Mott-Hubbard system, thus calling for a deeper theoretical study to reexamine the magnetic field tuning of Mott systems with magnetic and electronic instabilities and spin-lattice-charge coupling. This study further provides a model approach to search for CMR systems other than manganites, such as Mott insulators in the vicinity of the boundary between competing phases.


Comparison of short- and long-acting benzodiazepine-receptor agonists with different receptor selectivity on motor coordination and muscle relaxation following thiopental-induced anesthesia in mice.
In this study, we compared the effects of Type I benzodiazepine receptor-selective agonists (zolpidem, quazepam) and Type I/II non-selective agonists (zopiclone, triazolam, nitrazepam) with either an ultra-short action (zolpidem, zopiclone, triazolam) or long action (quazepam, nitrazepam) on motor coordination (rota-rod test) and muscle relaxation (traction test) following the recovery from thiopental-induced anesthesia (20 mg/kg) in ddY mice. Zolpidem (3 mg/kg), zopiclone (6 mg/kg), and triazolam (0.3 mg/kg) similarly caused an approximately 2-fold prolongation of the thiopental-induced anesthesia. Nitrazepam (1 mg/kg) and quazepam (3 mg/kg) showed a 6- or 10-fold prolongation of the anesthesia, respectively. Zolpidem and zopiclone had no effect on the rota-rod and traction test. Moreover, zolpidem did not affect motor coordination and caused no muscle relaxation following the recovery from the thiopental-induced anesthesia. However, zopiclone significantly impaired the motor coordination at the beginning of the recovery. Triazolam significantly impaired the motor coordination and muscle relaxant activity by itself, and these impairments were markedly exacerbated after the recovery from anesthesia. Nitrazepam and quazepam significantly impaired motor coordination, and the impairments were exacerbated after the recovery. These results suggest that the profile of recovery of motor coordination and muscle flaccidity after co-administration of benzodiazepine-receptor agonists and thiopental is related to the half-life and selectivity for the benzodiazepine-receptor subtypes.


A simplified technique for making an interocclusal record in fixed prosthodontics.
A technique for using flowable composite resin for making interocclusal records in cases involving fixed prosthodontics is described. The precise relation of maxillary and mandibular casts is an essential step in developing accurate occlusion in fixed prosthodontics. This technique consists of direct intraoral fabrication of transfer copings and an interocclusal record using flowable, light-activated composite resin. The technique is simple, does not require advance preparation and can be done during the final impression appointment.


Reduction of benzophenone by SmI2: the role of proton donors in determining product distribution.
[reaction: see text] Reduction of benzophenone by SmI2 yields benzopinacol. Addition of proton donors results in an initial increase in the amount of the benzhydrol formed. However, the ratio benzhydrol/benzopinacol reaches a maximum, decreases, and then levels off as the proton donor concentration is further increased. The position of the maximum and its height depend on the proton donor concentration and its kinetic acidity. The momentary concentration of the intermediate radicals governs the product distribution.


In vitro cytokine release from human peripheral blood mononuclear cells in the assessment of the immunotoxic potential of chemicals.
Alternative methods to the use of animals in testing of chemicals are needed. We investigated if the immunotoxic potential of 12 dietary toxicants could be predicted from effects on cytokine release from human peripheral blood mononuclear cells (PBMC) after in vitro exposure. Nine cytokines were selected to reflect different types of immune responses. The toxicants were classified as immunotoxic or non-immunotoxic substances according to the published in vivo data. Isolated human PBMC were exposed for 20 h to three concentrations of each of the 12 substances in the presence of human liver S9 fraction. After further incubation of PBMC in fresh medium containing the mitogen phytohemagglutinin (PHA, 10 μg/ml) for 48 h, release of the nine selected cytokines into the supernatant as well as cell proliferation were measured by Luminex technology™ and the BrdU incorporation assay, respectively. All 12 substances investigated affected the release of one or more cytokines, and each of the substances showed different cytokine release patterns. Within the limitations of the study design, the present study suggests that the effect of the substances on mitogen-induced cytokine release from PBMC cannot predict their immunotoxic potential, but may be useful in mechanistic studies.


In Situ Generation of Fluorescent Copper Nanoclusters Embedded in Monolithic Eggshell Membrane: Properties and Applications.
Luminescent metal nanoclusters have attracted considerable research attention in recent years due to their unique properties and extensive usage in many fields. Three different synthetic routes were developed to in situ generate orange and red emitting copper nanoclusters embedded in monolithic eggshell membrane (Cu NCs@ESM) using different reducing reagents including N₂H₄·H₂O, NH₂OH·HCl and Vitamin C at room temperature for the first time. The routes are extremely facile, low-cost and versatile. The obtained Cu NCs@ESM nanocomposites exhibit excellent photostability and chemical stability, laying the foundation for various practical applications. Fluorescent surface patterning was demonstrated based on the proposed strategy easily. Significantly, the Cu NCs@ESM shows selective fluorescence quenching response to Hg2+ ions and good catalytic activity for methylene blue (MB) reduction degradation making it ideal as portable sensing strip and recyclable catalyst. The work provides a general strategy for the fabrication of other various monolithic nanomaterials with potential applications.


The influence of heel height on vertical ground reaction force during landing tasks in recreationally active and athletic collegiate females.
To determine if heel height alters vertical ground reaction forces (vGRF) when landing from a forward hop or drop landing. Increased vGRF during landing are theorized to increase ACL injury risk in female athletes. Fifty collegiate females performed two single-limb landing tasks while wearing heel lifts of three different sizes (0, 12 & 24 mm) attached to the bottom of a athletic shoe. Using a force plate, peak vGRF at landing was examined. Repeated measures ANOVAs were used to determine the influence of heel height on the dependent measures. Forward hop task- Peak vGRF (normalized for body mass) with 0 mm, 12 mm, and 24 mm lifts were 2.613±0.498, 2.616±0.497 and 2.495±0.518% BW, respectively. Significant differences were noted between 0 and 24 mm lift (p<.001) and 12 and 24 mm lifts (p=.004), but not between the 0 and 12 mm conditions (p=.927). Jump-landing task- No significant differences were found in peak vGRF (p=.192) between any of the heel lift conditions. The addition of a 24 mm heel lift to the bottom of a sneaker significantly alters peak vGRF upon landing from a unilateral forward hop but not from a jumping maneuver.


Impact of targeted oral ganciclovir prophylaxis for transplant recipients of livers from cytomegalovirus-seropositive donors.
Symptomatic cytomegalovirus (CMV) infection can cause significant morbidity and occasional mortality after liver transplantation. In a previous audit, we showed that donor CMV seropositivity (D+) was a risk factor for symptomatic infection, and we estimated the likely clinical and financial impact of 14 weeks of oral ganciclovir prophylaxis given to recipients of CMV-seropositive organs. In August 2001, we adopted this policy of targeted oral ganciclovir prophylaxis for recipients of CMV-seropositive livers. The additional costs of adopting targeted prophylaxis policy for 1 year, patient and doctor compliance with the new strategy, and its clinical impact were analysed. Targeted prophylaxis reduced the incidence of symptomatic CMV infection from 9.5% (in the earlier cohort that did not receive prophylaxis) to 5.8% (P = NS). Symptomatic infection was not observed in CMV-seropositive recipients of CMV-seropositive donor livers (P = 0.06 for comparison of the 2 cohorts), but the incidence of symptomatic infection in the CMV-seronegative recipients of CMV-seropositive organs did not change. However, symptomatic infection appeared to be less severe and was delayed by ganciclovir prophylaxis (median time from transplantation to symptom onset 96 vs. 39 days without prophylaxis). Death attributable to CMV infection was not observed in the cohort that received prophylaxis. The additional cost associated with implementation of the prophylaxis strategy was 108,068 pounds sterlings. Targeted CMV prophylaxis with oral ganciclovir reduces the incidence and severity of symptomatic infection and appears to be a cost-effective means of improving outcome following liver transplantation.


A novel procedure for total nucleic acid extraction from small numbers of Eimeria species oocysts.
A series of experiments were performed in an attempt to extract genomic DNA from a small number of Eimerian oocysts. Sonication, ammonia, ethanol and lysozyme were all found to be unsuitable for the digestion of Eimeria oocysts. The chemicals and enzyme given were not capable of either disruption or digestion of oocysts for nucleic acid extraction. They had the capability of penetrating the oocyst wall but could not break-up the oocyst wall. It is impossible to obtain nucleic acid from Eimeria oocysts if the wall is not broken-up. In this study oocyst disruption was achieved using a simple but highly effective treatment regime involving sodium hypochlorite treatment, osmotic shock and proteinase K digestion. Following the disruption of the oocyst walls, a commercially available nucleic acid purification kit (Wizard DNA Purification Kit, Promega) can be used to prepare high quality nucleic acid.


[Immunoenzyme analysis of insulin antibodies in human blood serum].
Indirect solid-phase enzyme immunoassay (EIA) was used for the titration of antibodies to insulin in human blood sera. The modification suggested by the authors permits assessing the immunoglobulins G and M insulin-binding ability. The technique was optimized for all the stages of analysis and a method for estimating the insulin-binding ability of IgG in the sera diluted 1:80 and of IgM in the sera diluted 1:320 was developed. Fifty blood sera of patients with insulin-dependent diabetes mellitus were analyzed. EIA results were in good correlation with the findings of radioimmunoassay.


Novel intronic DICER1 variation associated with pleuropulmonary blastoma in two siblings.
Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies associated with DICER1 variants. We present two cases, a 2-year-old girl with upper respiratory tract symptoms as well as a 6-month-old girl sibling undergoing screening due to family history of malignancy. Imaging of the 2-year-old girl revealed a large mass filling the right hemithorax which was determined to be a type II PPB after pathological examination. Imaging of the 6-month-old sibling demonstrated a small cystic lesion in the posterior basal segment of the right lower lobe which was determined to be a type 1r PPB after pathological examination. The 2-year-old girl received adjuvant chemotherapy while the baby sister underwent resection alone and both are alive and well at 12 months and 7 months, respectively. Sequence analysis in both cases confirmed the same DICER1 variation, c.2437-2A>G (likely pathogenic), which has not been previously described in the literature.


Mesalazine-induced airway obstruction: Utility of pulmonary function testing in drug-induced lung diseases.
Mesalazine is a standard therapeutic agent for the treatment of inflammatory bowel diseases. A rare case of mesalazine-induced airway obstruction documented by pulmonary function testing is reported herein. The patient had Crohn's disease and was treated with mesalazine; she subsequently developed a high fever, cough, and chest pain with centrilobular nodular shadows on chest computed tomography (CT). After cessation of mesalazine, the abnormal CT findings as well as the decreased forced expiratory volume in 1 second improved. Based on these findings, pulmonary function testing appears to be a useful tool, even in the acute phase, along with chest CT in drug-induced lung diseases.


Commentary: A social environment approach to promotive and protective practice in childhood resilience--reflections on Ungar (2014).
The field of mental health and psychosocial support for children in humanitarian emergencies has been evolving rapidly. A decade ago, researchers and practitioners frequently took a deficits approach that emphasized problems such as trauma, particularly post-traumatic stress disorder (PTSD), in zones of armed conflict. Assessments focused on PTSD and typically led to the provision of curative responses such as Western psychotherapies as the first response for the affected population. Practitioners expressed diverse concerns about this approach, including its narrow, medicalized definition of the problem (mental disorder), the unsustainability of the programs it generated, the relative inattention to the context, the privileging of individual over systemic approaches, and the lack of cultural sensitivity. For these and other reasons, humanitarian practitioners have increasingly favored a resilience approach that features the agency of children, families, and communities and seeks to build upon existing assets or strengths. Already there is evidence of the effectiveness of numerous interventions that embody a resilience approach. Yet resilience approaches have been limited by a lack of conceptual clarity and ongoing questions about how to assess and measure it. In this context, Michael Ungar's Practitioner Review is an important contribution to practice.


Spondylometaphyseal dysplasia-Sedaghatian type.
We present the radiological findings in two unrelated cases with spondylometaphyseal dysplasia type Sedaghatian. We review the literature and identify additional anomalies including disproportionately long fibulae, dysharmonious maturation and turricephaly.


An automated bladder volume measurement algorithm by pixel classification using random forests.
Residual bladder volume measurement is a very important marker for patients with urinary retention problems. To be able to monitor patients with these conditions at the bedside by nurses or in an out patient setting by general physicians, hand held ultrasound devices will be extremely useful. However to increase the usage of these devices by non traditional users, automated tools that can aid them in the scanning and measurement process will be of great help. In our paper, we have developed a robust segmentation algorithm to automatically measure bladder volume by segmenting bladder contours from sagittal and transverse ultrasound views using a combination of machine learning and active contour algorithms. The algorithm is tested on 50 unseen images and 23 transverse and longitudinal image pairs and the performance is reported.


Reverse-phase protein microarrays: application to biomarker discovery and translational medicine.
Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Kinases are important drug targets, as such kinase network information could become the basis for development of therapeutic strategies for improving treatment outcome. An urgent clinical goal is to identify functionally important molecular networks associated with subpopulations of patients that may not respond to conventional combination chemotherapy. Reverse-phase protein microarrays are a technology platform designed for quantitative, multiplexed analysis of specific phosphorylated, cleaved, or total (phosphorylated and nonphosphorylated) forms of cellular proteins from a limited amount of sample. This class of microarray can be used to interrogate cellular samples, serum or body fluids. This review focuses on the application of reverse-phase protein microarrays for translational research and therapeutic drug target discovery.


Hybrid Lipids Inspired by Extremophiles and Eukaryotes Afford Serum-Stable Membranes with Low Leakage.
This paper presents a new hybrid lipid that fuses the ideas of molecular tethering of lipid tails used by archaea and the integration of cholesterol groups used by eukaryotes, thereby leveraging two strategies employed by nature to increase lipid packing in membranes. Liposomes comprised of pure hybrid lipids exhibited a 5-30-fold decrease in membrane leakage of small ions and molecules compared to liposomes that used only one strategy (lipid tethering or cholesterol incorporation) to increase membrane integrity. Molecular dynamics simulations reveal that tethering of lipid tails and integration of cholesterol both reduce the disorder in lipid tails and time-dependent variance in area per lipid within a membrane, leading to tighter lipid packing. These hybrid lipid membranes have exceptional stability in serum, yet can support functional ion channels, can serve as a substrate for phospholipase enzymes, and can be used for liposomal delivery of molecules into living cells.


First Report of Powdery Mildew Caused by Golovinomyces ambrosiae on Xanthium orientale in Korea.
Xanthium orientale L. (syn. Xanthium canadense Mill., Asteraceae), known as cocklebur, is an annual weed native to North America, which is now a neophyte distributed throughout the world. This plant was accidentally introduced to Korea in the late 1970s ( So et al. 2008) and is considered a problematic exotic weed in orchards, for which many herbicides are ineffective (Kim et al. 2020). In September 2018, powdery mildew was observed on X. orientale in Jeju, Korea. The disease incidence ranged from 40 to 60%. Voucher specimens were deposited in the Korea University Herbarium (Accession No. KUS-F30795) and Kunsan National University Herbarium (KSNUH1988). Symptoms appeared as round to irregular white patches with abundant hyphal growth on the leaf surface. Hyphal appressoria were nipple-shaped, and 3 to 6 μm diam. Conidiophores (n = 30) were 145 to 206 × 9 to 11.6 µm and produced 2 to 5 immature conidia in chains with a sinuate outline. Foot-cells of the conidiophores were straight, cylindrical, and 43 to 100.9 μm long. Conidia (n = 30) were ellipsoid-ovoid, doliiform to somewhat limoniform, 25.2 to 31.8 × 13.6 to 16.8 μm (l/w 1.6 to 2.1), and devoid of distinct fibrosin bodies. The morphological characteristics corresponded to those of Golovinomyces ambrosiae (Schwein.) U. Braun & R.T.A. Cook (Braun and Cook 2012, under Golovinomyces spadiceus (Beck. & M.A. Curtis) U. Braun; Qiu et al. 2020). To confirm the identity of the causal fungus, the internal transcribed spacer (ITS), large subunit (LSU) (Bradshaw and Tobin 2020), the intergenic spacer (IGS) of rDNA, and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene (Bradshaw et al. 2022) were amplified for a herbarium specimen (KUS-F30795). A BLASTn search of these sequences revealed 100% identity with reference sequences of G. ambrosiae on diverse Asteraceae plants (AB077644 for ITS, AB077643 for LSU, ON361171 for IGS, and ON075648 for GAPDH). However, there was a single nucleotide difference on both the IGS and GAPDH sequences when compared to the closely related species Golovinomyces latisporus. The sequences were deposited in GenBank (Accession No. OQ165157 (ITS), OQ165164 (LSU), OR050524 (IGS), and OR086076 (GAPDH)). Phylogenetic analyses of ITS, LSU, IGS, and GAPDH sequences revealed the Korean sample formed a well-supported group with other G. ambrosiae sequences, confirming its identity. A pathogenicity test was performed through inoculation by gently pressing diseased leaves onto the leaves of five healthy plants. Five non-inoculated plants served as controls. All plants were maintained in a greenhouse at 25±2°C. Powdery mildew colonies developed on the inoculated plants after ten days, whereas the control plants remained symptomless. The fungus present on the inoculated leaves was morphologically identical to that observed on the initially diseased leaves, fulfilling Koch's postulates. Powdery mildew on X. orientale has previously been reported as Golovinomyces cichoracearum (≡ Erysiphe cichoracearum) sensu lato in the USA, G. ambrosiae (= G. spadiceus) throughout all continents, and Podosphaera fusca sensu lato (now P. xanthii) in Korea (Braun and Cook 2012; Farr and Rossman 2023). To date, powdery mildew in Korea has been reported only on Xanthium strumarium as G. cichoracearum s. lat. and Podosphaera xanthii (KSPP 2022). To our knowledge, this is the first report of powdery mildew caused by G. ambrosiae on X. orientale in Korea.


[The problem of usefulness of the philosophical concept of disease in medicine].
This work focuses on contemporary discussions devoted to the general concept of disease and its relevance to clinical practice. Some authors (e.g., Hesslow) argue against a key role of the general concept of disease in clinical decision-making. Other authors (Pellegrino, Clouser, Culver, and Gert) emphasize the significance of the concept of disease in public health and in the methodology of medical practice.


Assessment of Posterior and Middle Facet Subluxation of the Subtalar Joint in Progressive Flatfoot Deformity.
Adult acquired flatfoot deformity (AAFD) is a complex 3-dimensional pathology characterized by peritalar subluxation (PTS) of the hindfoot. For many years, PTS was measured at the posterior facet of the subtalar joint. More recently, subluxation of the middle facet has been proposed as a more accurate and reliable marker of symptomatic AAFD, enabling earlier detection. The objective of this study was to compare the amount of subluxation between the medial and posterior facets in patients with AAFD. In this institutional review board-approved retrospective comparative study, a total of 76 patients with AAFD (87 feet) who underwent standing weightbearing computed tomography (WBCT) as a standard baseline assessment of their foot deformity were analyzed. Two blinded fellowship-trained orthopedic foot and ankle surgeons with >10 years of experience measured subtalar joint subluxation (as a percentage of joint uncoverage) at the both posterior and middle facets. One of the readers also measured the foot and ankle offset (FAO). PTS measurements were performed at the sagittal midpoint of the articular facets using coronal plane WBCT images. Intra- and interobserver agreement was measured for PTS measurements using the intraclass correlation coefficient (ICC). The intermethod agreement between the posterior and middle facet subluxation was assessed using Spearman's correlation and bivariate analysis. Paired comparison of the measurements was performed using the Wilcoxon test. A multivariate analysis and a partition prediction model were used to assess influence of PTS measurements on FAO values. P values of <.05 were considered significant. ICCs for intra- and interobserver reliabilities were 0.97 and 0.93, respectively, for posterior and 0.99 and 0.97, respectively, for middle facet subluxation. The intermethod Spearman's correlation between subluxation of the posterior and middle facets was measured at 0.61. In a bivariate analysis, both measurements were found to be significantly and linearly correlated (P < .0001; R2 = 0.42). Measurements of middle facet subluxation were found to be significantly higher than those for posterior facet subluxation, with a median difference (using the Hodges-Lehman factor) of 17.7% (P < .001; 95% CI, 10.9%-23.6%). We also found that for every 1% increase in posterior facet subluxation there was a corresponding 1.6-fold increase in middle facet subluxation. Only middle facet subluxation measurements were found to significantly influence FAO calculations (P = .003). The partition prediction model demonstrated that a middle facet subluxation value of 43.8% represented an important threshold for increased FAO. This study is the first to compare WBCT measurements of subtalar joint subluxation at the posterior and middle facets as markers of PTS in patients with AAFD. We found a positive linear correlation between the measurements, with subluxation of the middle facet being significantly more pronounced than that of the posterior facet by an average of almost 18%. This suggests that middle facet subluxation may provide an earlier and more pronounced marker of progressive PTS in patients with AAFD. Level III, retrospective comparative cohort study.


SynBio2Easy-a biologist-friendly tool for batch operations on SBOL designs with Excel inputs.
Practical delivery of Findable, Accessible, Reusable and Interoperable principles for research data management requires expertise, time resource, (meta)data standards and formats, software tools and public repositories. The Synthetic Biology Open Language (SBOL2) metadata standard enables FAIR sharing of the designs of synthetic biology constructs, notably in the repository of the SynBioHub platform. Large libraries of such constructs are increasingly easy to produce in practice, for example, in DNA foundries. However, manual curation of the equivalent libraries of designs remains cumbersome for a typical lab researcher, creating a barrier to data sharing. Here, we present a simple tool SynBio2Easy, which streamlines and automates operations on multiple Synthetic Biology Open Language (SBOL) designs using Microsoft Excel® tables as metadata inputs. The tool provides several utilities for manipulation of SBOL documents and interaction with SynBioHub: for example, generation of a library of plasmids based on an original design template, bulk deposition into SynBioHub, or annotation of existing SBOL component definitions with notes and authorship information. The tool was used to generate and deposit a collection of 3661 cyanobacterium Synechocystis plasmids into the public SynBioHub repository. In the process of developing the software and uploading these data, we evaluated some aspects of the SynBioHub platform and SBOL ecosystem, and we discuss proposals for improvement that could benefit the user community. With software such as SynBio2Easy, we aim to deliver a user-driven tooling to make FAIR a reality at all stages of the project lifecycle in synthetic biology research. Graphical Abstract.


Characteristics of government workers and association with diabetes and hypertension in the Cook Islands.
Twenty government departments in Rarotonga, Cook Islands. To determine the characteristics, presence of selected non-communicable disease (NCD) risk factors and prevalence of diabetes mellitus (DM) and hypertension among government workers who participated in 'wellness checks' in 2012. Cross-sectional study involving analysis of survey data. Of 598 employees, 70% were aged 25-54 years and 55% were female. Two thirds were obese (body mass index ⩾30 kg/m(2)), and 76% had low levels of fruit and vegetable consumption. Of 50 (8.4%) participants diagnosed with DM (random blood glucose ⩾11 mmol/l, fasting ⩾7 mmol/l), 30 were self-reported and 20 were based on blood glucose. Of the 206 (34.4%) diagnosed with hypertension (systolic ⩾140 and/or diastolic ⩾90), 71 were self-reported and 135 were based on blood pressure measurements. Obesity was associated with hypertension (OR 2.79, 95%CI 1.4-5.4), but not with DM. No relationship was observed between fruit and vegetable consumption and presence or absence of DM or hypertension. This study identified a high prevalence of obesity and hypertension among government employees in the Cook Islands, risk factors that are associated with NCDs such as DM and cardiovascular disease. 'Wellness checks' pave the way for interventions in workplace settings to prevent and better manage these diseases through early diagnosis, risk management, treatment and supportive public health policies.


Model averaging methods for the evaluation of dose-response model uncertainty when assessing the suitability of studies for estimating risk.
This paper describes the use of multiple models and model averaging for considering dose-response uncertainties when extrapolating low-dose risk from studies of populations with high levels of exposure. The model averaging approach we applied builds upon innovative methods developed by the U.S. Food and Drug Administration (FDA), principally through the relaxing of model constraints. The relaxing of model constraints allowed us to evaluate model uncertainty using a broader set of model forms and, within the context of model averaging, did not result in the extreme supralinearity that is the primary concern associated with the application of individual unconstrained models. A study of the relationship between inorganic arsenic exposure to a Taiwanese population and potential carcinogenic effects is used to illustrate the approach. We adjusted the reported number of cases from two published prospective cohort studies of bladder and lung cancer in a Taiwanese population to account for potential covariates and less-than-lifetime exposure (for estimating effects on lifetime cancer incidence), used bootstrap methods to estimate the uncertainty surrounding the µg/kg-day inorganic arsenic dose from drinking water and dietary intakes, and fit multiple models weighted by Bayesian Information Criterion to the adjusted incidence and dose data to generate dose-specific mean, 2.5th and 97.5th percentile risk estimates. Widely divergent results from adequate model fits for a broad set of constrained and unconstrained models applied individually and in a model averaging framework suggest that substantial model uncertainty exists in risk extrapolation from estimated doses in the Taiwanese studies to lower doses more relevant to countries like the U.S. that have proportionally lower arsenic intake levels.


[Screening of producers of bacteriocin-like substances active against Pseudomonas aeruginosa].
The strains (n = 94) of 16 Pseudomonas species have been screened for producers of substances active against Pseudomonas aeruginosa. Investigated cultures were divided into two groups. The majority of Pseudomonas species have been included in the first group. These species were able to produce substances with low and medium activity spectrum. In the first group P. mendocina, P. fragi and P. taetrolens lysates were the most active and influenced 30-50% of indicator cultures. Only P. aeruginosa strains belong to the second group. The microorganisms of this group were able to produce substances with considerably higher activity spectrum. Among all investigated pseudomonades four P. aeruginosa strain lysates possessed the highest activity and were active against more than 75% of used cultures. It was shown that the main active killer components of these lysates belonged to low-weight pyocins.


Policy Research Challenges in Comparing Care Models for Dual-Eligible Beneficiaries.
Providing affordable, high-quality care for the 10 million persons who are dual-eligible beneficiaries of Medicare and Medicaid is an ongoing health-care policy challenge in the United States. However, the workforce and the care provided to dual-eligible beneficiaries are understudied. The purpose of this article is to provide a narrative of the challenges and lessons learned from an exploratory study in the use of clinical and administrative data to compare the workforce of two care models that deliver home- and community-based services to dual-eligible beneficiaries. The research challenges that the study team encountered were as follows: (a) comparing different care models, (b) standardizing data across care models, and (c) comparing patterns of health-care utilization. The methods used to meet these challenges included expert opinion to classify data and summative content analysis to compare and count data. Using descriptive statistics, a summary comparison of the two care models suggested that the coordinated care model workforce provided significantly greater hours of care per recipient than the integrated care model workforce. This likely represented the coordinated care model's focus on providing in-home services for one recipient, whereas the integrated care model focused on providing services in a day center with group activities. The lesson learned from this exploratory study is the need for standardized quality measures across home- and community-based services agencies to determine the workforce that best meets the needs of dual-eligible beneficiaries.


Stereospecificity of ketoreductase domains of the 6-deoxyerythronolide B synthase.
6-Deoxyerythronolide B synthase (DEBS) is a modular polyketide synthase (PKS) responsible for the biosynthesis of 6-dEB (1), the parent aglycone of the broad spectrum macrolide antibiotic erythromycin. Individual DEBS modules, which contain the catalytic domains necessary for each step of polyketide chain elongation and chemical modification, can be deconstructed into constituent domains. To better understand the intrinsic stereospecificity of the ketoreductase (KR) domains, an in vitro reconstituted system has been developed involving combinations of ketosynthase (KS)-acyl transferase (AT) didomains with acyl-carrier protein (ACP) and KR domains from different DEBS modules. Incubations with (2S,3R)-2-methyl-3-hydroxypentanoic acid N-acetylcysteamine thioester (2) and methylmalonyl-CoA plus NADPH result in formation of a reduced, ACP-bound triketide that is converted to the corresponding triketide lactone 4 by either base- or enzyme-catalyzed hydrolysis/cyclization. A sensitive and robust GC-MS technique has been developed to assign the stereochemistry of the resulting triketide lactones, on the basis of direct comparison with synthetic standards of each of the four possible diasteromers 4a-4d. Using the [KS][AT] didomains from either DEBS module 3 or module 6 in combination with KR domains from modules 2 or 6 gave in all cases exclusively (2R,3S,4R,5R)-3,5-dihydroxy-2,4-dimethyl-n-heptanoic acid-delta-lactone (4a). The same product was also generated by a chimeric module in which [KS3][AT3] was fused to [KR5][ACP5] and the DEBS thioesterase [TE] domain. Reductive quenching of the ACP-bound 2-methyl-3-ketoacyl triketide intermediate with sodium borohydride confirmed that in each case the triketide intermediate carried only an unepimerized d-2-methyl group. The results confirm the predicted stereospecificity of the individual KR domains, while revealing an unexpected configurational stability of the ACP-bound 2-methyl-3-ketoacyl thioester intermediate. The methodology should be applicable to the study of any combination of heterologous [KS][AT] and [KR] domains.


Science, politics, and ideology in the campaign against environmental tobacco smoke.
The issue of environmental tobacco smoke (ETS) and the harms it causes to nonsmoking bystanders has occupied a central place in the rhetoric and strategy of antismoking forces in the United States over the past 3 decades. Beginning in the 1970s, anti-tobacco activists drew on suggestive and incomplete evidence to push for far-reaching prohibitions on smoking in a variety of public settings. Public health professionals and other antismoking activists, although concerned about the potential illness and death that ETS might cause in nonsmokers, also used restrictions on public smoking as a way to erode the social acceptability of cigarettes and thereby reduce smoking prevalence. This strategy was necessitated by the context of American political culture, especially the hostility toward public health interventions that are overtly paternalistic.


Sarcoidosis presenting as a loss of weight with preserved appetite.
Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology affecting a wide range of organs and is characterised by the presence of noncaseating granulomas. It has rarely been reported in Sri Lanka. This case describes a 36-year-old male presenting with a loss of weight despite a preserved appetite. He had evidence of sarcoidosis with pulmonary, lymph node, eye, hepatosplenomegaly, thyroid and parotid gland involvement with hypercalcaemia. He was successfully treated with glucocorticoids.


Galanin promotes neuronal differentiation in murine subventricular zone cell cultures.
Neural stem cells of the subventricular zone (SVZ) represent a potentially important source of surrogate cells for the treatment of brain damage. Proper use of these cells for neuronal replacement depends on the ability to drive neuronal differentiation. Several neuromodulators stimulate neurogenesis. Here we examined the effects of the neuropeptide galanin, on neuronal differentiation in murine SVZ cultures. SVZ neurospheres obtained from early postnatal mice were treated with 10 nM to 2 μM galanin. Galanin promoted neuronal differentiation, increasing numbers of NeuN-, vesicular GABA transporter- and tyrosine hydroxylase-expressing neurons. In contrast, galanin neither affected cell proliferation assessed by BrdU incorporation nor cell death evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Neuronal differentiation was further confirmed at the functional level by measuring [Ca(2+)]i variations in single SVZ cells after KCl and histamine stimulations to distinguish neurons from immature cells. Galanin treatment increased the numbers of neuronal-like responding cells compared to immature cells. Using selective agonists (M617, AR-M1896) and antagonists (galantide, M871) for galanin receptors 1 and 2, we showed that both galanin receptors mediated neuronal differentiation. Early proneuronal effects of galanin included positive regulation of the transcription factor neurogenin-1 (Ngn1). In addition, galanin promoted axonogenesis and dendritogenesis, increasing both the length of phosphorylated stress-activated protein kinase- and Tau-positive axons and the numbers of microtubule associated protein-2 (MAP-2)-labelled dendrites. Moreover, galanin inhibited SVZ cell migration in the transwell assay. Our results show a proneurogenic effect of galanin and open new perspectives for future applications in stem cell-based therapies for neuronal replacement.


Incontinence-Associated Dermatitis: State of the Science and Knowledge Translation.
This review of the literature updates and considers the evidence on incontinence-associated dermatitis (IAD). Best practice strategies for the management of skin damage from IAD (both prevention and treatment) are provided. A mnemonic to help clinicians translate IAD evidence into practice is introduced. Workplace experiences supplement this evidence synthesis. Approaches to assist in translation of this knowledge and evidence into practice are also provided.


The Development and Validation of an Online Spatial Network Measure.
Planning is an essential cognitive process of executive functions and is considered as one of the most important brain functions. Planning has been extensively studied in the field of neuropsychology, but there is a lack of computerized assessment tools of planning ability that are easily accessible to researchers and clinicians. The present study aims to validate a newly developed online spatial network test that is designed for both clinical and nonclinical populations. Exploratory factor analysis revealed a unidimensional factorial structure with moderate to high internal consistency in the test. Two-parameter logistic item response theory analysis showed acceptable item and model fit and no violation of the local independence assumption. The overall success rate exhibited a positive correlation with the performance of planning before attempting to solve the items. After correcting for attenuation, moderate to high correlations were found between the spatial network test and the International Cognitive Ability Resource 16 short form cognitive ability test and the automated perceptual maze test, respectively, demonstrating convergent, discriminant, and criterion validity. Future directions and potential applications of the spatial network test as an assessment tool to measure planning for researchers and clinicians are discussed in the end.


The fluoridation status of U.S. public water supplies.
It has been 40 years since the first community in the United States added a regulated amount of fluoride to its public water supply to prevent tooth decay. Despite the proven benefits of fluoride, today only 61 percent of the U.S. population on public water supplies receives fluoridated water. Progress in fluoridating water is impeded by antifluoridation campaigns and a change in the way Federal funds are allocated for State and local fluoridation programs. Despite profluoridation efforts by the Public Health Service, American Dental Association, and other organizations, the well-publicized claims of fluoride hazards by opponents have prevented many communities from initiating water fluoridation and have caused other communities to discontinue their programs. The law and half a century of research are on the side of fluoridation, as are new scientific findings indicating that optimal amounts of fluoride may reduce the incidence or severity of osteoporosis.


Progression and recovery of Parkinsonism in a chronic progressive MPTP-induction model in the marmoset without persistent molecular and cellular damage.
Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in marmoset monkeys was used to model the prodromal stage of Parkinson's disease (PD), and to investigate mechanisms underlying disease progression and recovery. Marmosets were subcutaneously injected with MPTP for a period of 12weeks, 0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor behaviors were recorded before, during and after exposure. In addition, postmortem immunohistochemistry and proteomics analysis were performed. MPTP-induced parkinsonian clinical symptoms increased in severity during exposure, and recovered after MPTP administration was ended. Postmortem analyses, after the recovery period, revealed no alteration of the number and sizes of tyrosine hydroxylase (TH)-positive dopamine (DA) neurons in the substantia nigra. Also levels of TH in putamen and caudate nucleus were unaltered, no differences were observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and proteomics analysis revealed no global changes in protein expression in these brain areas between treatment groups. Our findings indicate that parkinsonian symptoms can occur without detectable damage at the cellular or molecular level. Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and treated early.


Adsorbate-Induced Adatom Formation on Lithium, Iron, Cobalt, Ruthenium, and Rhenium Surfaces.
Recent experimental and theoretical studies have demonstrated the reaction-driven metal-metal bond breaking in metal catalytic surfaces even under relatively mild conditions. Here, we construct a density functional theory (DFT) database for the adsorbate-induced adatom formation energy on the close-packed facets of three hexagonal close-packed metals (Co, Ru, and Re) and two body-centered cubic metals (Li and Fe), where the source of the ejected metal atom is either a step edge or a close-packed surface. For Co and Ru, we also considered their metastable face-centered cubic structures. We studied 18 different adsorbates relevant to catalytic processes and predicted noticeably easier adatom formation on Li and Fe compared to the other three metals. The NH3- and CO-induced adatom formation on Fe(110) is possible at room temperature, a result relevant to NH3 synthesis and Fischer-Tropsch synthesis, respectively. There also exist other systems with favorable adsorbate effects for adatom formation relevant to catalytic processes at elevated temperatures (500-700 K). Our results offer insight into the reaction-driven formation of metal clusters, which could play the role of active sites in reactions catalyzed by Li, Fe, Co, Ru, and Re catalysts.


Optical negative refraction in ferrofluids with magnetocontrollability.
We numerically demonstrate optical negative refraction in ferrofluids containing isotropic Fe3O4 nanoparticles, each having an isotropic Ag shell, in the presence of an external dc magnetic field H. The all-angle broadband optical negative refraction with magnetocontrollability arises from H-induced chains or columns. They result in hyperbolic equifrequency contour for transverse magnetic waves propagating in the system. The finite element simulations verify the analyses using the effective medium approximation. Experimental demonstration and potential applications are suggested and discussed.


Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/β-catenin pathway.
Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active β-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance. Higher cAMP response elements and Tcf/Lef transcription activities were shown in the drug-resistant cancer cells. However, expression of Wnt target genes and CRE activities was downregulated in Wnt5A shRNA stably-transfected MES-SA/Dx5 cells. Cell viability of the drug-resistant cancer cells was also reduced by doxorubicin treatment and Wnt5A shRNA transfection, or by Wnt5A depletion. The in vitro data were supported by immunohistochemical analysis of 24 paired breast cancer biopsies obtained pre- and post-chemotherapeutic treatment. Wnt5A, VEGF and/or ABCB1 were significantly overexpressed after treatment, consistent with clinical chemoresistance. Taken together, the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and β-catenin-related genes in antagonizing the toxic effects of doxorubicin in the MDR cell lines and in clinical breast cancer samples.